1. Field of the Invention
The present invention relates to methods for detecting the presence of certain sulfhydryl-containing compounds in a biological test sample by either forming a derivative of the sulfhydryl-containing compound or by stabilizing the sulfhydryl-containing compound. This invention also relates to novel derivatives of the sulfhydryl-containing compounds.
2. State of the Art
Commonly-assigned U.S. Publication Nos. 2008/0269305 and 2009/0023228, both to Allegretti et al. filed on Apr. 23, 2008, disclose novel imidazole compounds that are useful as hypertensive agents, the disclosures of which are incorporated herein by reference. In particular, the following sulfhydryl-containing compounds are specifically disclosed in these applications:    4′-{4-ethyl-5-[((S)-2-mercapto-4-methylpentanoylamino)methyl]-2-propoxyimidazol-1-ylmethyl}-3′-fluorobiphenyl-2-carboxylic acid;    4′-{4-ethyl-5-[((S)-2-mercapto-4-methylpentanoylamino)methyl]-2-propoxyimidazol-1-ylmethyl}-2′-fluorobiphenyl-2-carboxylic acid;    4′-{2-ethoxy-4-ethyl-5-[((S)-2-mercapto-4-methylpentanoylamino)methyl]-imidazol-1-ylmethyl}-3′-fluorobiphenyl-2-carboxylic acid; and    4′-{4-cyclopropyl-2-ethoxy-5-[((S)-2-mercapto-4-methylpentanoylamino)-methyl]imidazol-1-ylmethyl}-3′-fluorobiphenyl-2-carboxylic acid.
For many reasons, it is often necessary or desirable to detect or accurately measure the amount of a compound, such as a therapeutic agent, in a biological test sample, such as blood or plasma. However, compounds that contain a sulfhydryl (—SH) group, such as those identified above, can be difficult to detect or measure accurately since the sulfhydryl group may be reactive under certain conditions. For example, in plasma samples, the sulfhydryl group can readily oxidize to form disulfide (—S—S—) containing homodimers or it can form heterodimers with other sulfhydryl groups present in circulating proteins found in plasma (for example, serum albumin, glutathione, and cysteine). In either case, the parent sulfhydryl-containing compound can be difficult to detect and, in particular, the amount or concentration of the parent sulfhydryl-containing compound in the sample can be difficult to measure accurately.